Expression of lectin-like oxidized low-density lipoprotein receptors during ischemia-reperfusion and its role in determination of apoptosis and left ventricular dysfunction.

Abstract

OBJECTIVES:

The goal of this study was to determine the role of lectin-like oxidized low-density lipoprotein receptors (LOX-1), a recently identified oxidized low-density lipoprotein (ox-LDL) receptor, in ischemia-reperfusion injury to the heart.

BACKGROUND:

Reactive oxygen species (ROS) released during ischemia-reperfusion oxidize low-density lipoproteins; LOX-1 is upregulated by ox-LDL and ROS, and is involved in cell injury.

METHODS:

Anesthetized rats were subjected to left coronary artery ligation for 60 min (n = 10, ischemia group), or ischemia followed by 60 min of reperfusion (n = 30, ischemia-reperfusion group). Rats in the latter group were treated with saline, the LOX-1 blocking antibody JXT21 (10 mg/kg), or nonspecific anti-goat immunoglobulin G (IgG) (10 mg/kg). Ten other rats underwent thoracotomy without coronary ligation (sham control).

RESULTS:

Ischemia-reperfusion was associated with an increase in LOX-1 expression, lipid peroxidation and apoptosis, a large infarct area, and a decrease in left ventricular function (all, p < 0.01 vs. sham control and ischemia alone groups). Treatment of rats with LOX-1 antibody prevented ischemia-reperfusion-induced upregulation of LOX-1. Importantly, the LOX-1 antibody reduced apoptosis by 48%, lipid peroxidation by 39%, and myocardial infarct size by 45%, and improved left ventricular function (first derivative of pressure measured over time: -47% to -18%, p < 0.01). Nonspecific IgG had no effect.

CONCLUSIONS:

Lectin-like oxidized low-density lipoprotein receptors are upregulated during myocardial ischemia-reperfusion, and appear to be associated with apoptosis, necrosis, and left ventricular functional deterioration.

• Authors: Dayuan Li, Victor Williams, Ling Liu, Hongjiang Chen, Tatsuya Sawamura, Francesco Romeo, Jawahar L Mehta
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 41 Issue 6 Pg. 1048-55 (Mar 19 2003) ISSN: 0735-1097 [Print] United States
• PMID: 12651056 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• OLR1 protein, rat
• Olr1 protein, mouse
• Receptors, LDL
• Receptors, Oxidized LDL
• Scavenger Receptors, Class E

Topics

• Animals
• Apoptosis (genetics, physiology)
• Disease Models, Animal
• Gene Expression (genetics, physiology)
• Male
• Mice
• Mice, Inbred BALB C
• Necrosis
• Rats
• Rats, Sprague-Dawley
• Receptors, LDL (genetics, physiology)
• Receptors, Oxidized LDL
• Reperfusion Injury (genetics, pathology, physiopathology)
• Scavenger Receptors, Class E
• Ventricular Dysfunction, Left (genetics, pathology, physiopathology)